Supplementation of Heat-Treated Lactiplantibacillus plantarum nF1 Changes the Production of Short-Chain Fatty Acids in Healthy Infants.

Background: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods: The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results: The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively). Conclusions: Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.

Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age.

The most common causes of short stature (SS) in children are familial short stature (FSS) and idiopathic short stature (ISS). Recently, growth plate dysfunction has been recognized as the genetic cause of FSS or ISS. The aim of this study was to investigate monogenic growth failure in patients with ISS and FSS. Targeted exome sequencing was performed in patients categorized as ISS or FSS and the subsequent response to growth hormone (GH) therapy was analyzed. We found 17 genetic causes involving 12 genes (NPR2, IHH, BBS1, COL1A1, COL2A1, TRPS1, MASP1, SPRED1, PTPTN11, ADNP, NADSYN1, and CERT1) and 2 copy number variants. A genetic cause was found in 45.5% and 35.7% of patients with FSS and ISS, respectively. The genetic yield in patients with syndromic and non-syndromic SS was 90% and 23.1%, respectively. In the 11 genetically confirmed patients, a gain in height from -2.6 to -1.3 standard deviations after 2 years of GH treatment was found. The overall diagnostic yield in this study was 41.7%. We identified several genetic causes involving paracrine signaling, the extracellular matrix, and basic intracellular processes. Identification of the causative gene may provide prognostic evidence for the use of GH therapy in non-SGA children.

Prevalence of asthma in preterm and associated risk factors based on prescription data from the Korean National Health Insurance database.

We retrospectively analyzed National Health Insurance claims data (January 2002-December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.

Association between maternal weight gain during pregnancy and child's body mass index at preschool age.

BACKGROUND: Recent studies reported that prepregnancy body mass index (BMI) and weight gain during pregnancy affect birth weight and contribute to childhood obesity. However, no such data are available in Korea. PURPOSE: This study gathered data on weight gain during pregnancy and its impact on birth weight and childhood obesity in Korea. METHODS: We reviewed 1,753 singleton full-term babies born at CHA Bundang Medical Center in 2014-2016. We first review each maternal and baby factor based on prepregnancy BMI (underweight, normal, overweight/obese) and then divided them into low, normal, and excess gestational weight gain (GWG) groups based on the American Institute of Medicine (IOM) guidelines. We reviewed the characteristics of each group and analyzed the association between maternal GWG based on IOM guidelines and child BMI after 6 years. RESULTS: The maternal prepregnancy BMI group showed a significant difference in birth weight and child BMI at 6 years. As the prepregnancy BMI increased, the birth weight and BMI at 6 years also increased (P<0.001). Mean birth weight and child BMI at 6 years differed significantly among the GWG groups. Furthermore, excess postpartum weight gain increased the risk of childhood overweight and obesity (odds ratio, 2.21; 95% confidence interval, 1.40-3.49). CONCLUSION: Excess weight gain during pregnancy should be avoided due to its short- and long-term association with childhood obesity. Owing to the high prevalence of excess GWG and childhood obesity, excess weight gain during pregnancy can have significant public health implications.

Infantile Colic and the Subsequent Development of the Irritable Bowel Syndrome.

Background/Aims: Little is known about the association between infantile colic and the later onset of irritable bowel syndrome (IBS). Methods: This study examined all 917 707 children who were born in Korea between 2007 and 2008. Infantile colic was defined with 1 or more diagnoses of ICD-10 code R10.4 or R68.1 at the age of 5 weeks to 4 months, and infants with a diagnosis of infantile colic and without were allocated into the infantile colic group and the control group. IBS was defined as 2 or more diagnoses of ICD-10 code K58.X after 4 years of age. Each child was traced until 2017. The risk of IBS with infantile colic was evaluated using a Cox proportional hazards model with propensity score inverse probability of treatment weighting (IPTW). Results: After IPTW, 363 528 and 359 842 children were allocated to the control group and the infantile colic group, respectively. The infantile colic group had a higher risk of developing IBS in childhood (hazard ratio [95% CI], 1.12 [1.10 to 1.13]) than the control group. Moreover, the subgroup analyses according to the feeding status, birth weight, sex, or economic status, showed that the risk of IBS with former infantile colic remained statistically significant. Conclusions: Children with a diagnosis of infantile colic during the infant period had a significant risk of developing IBS after 4 years of age. Understanding the pathogenesis of infantile colic in the neonatal period may reduce the prevalence and severity of functional gastrointestinal disorders from childhood to adolescence to adulthood.

Changes to Gut Microbiota Following Systemic Antibiotic Administration in Infants.

Long-term antibiotic use can have consequences on systemic diseases, such as obesity, allergy, and depression, implicating the causal role of gut microbiome imbalance. However, the evaluation of the effect of antibiotics in early infancy on alterations to the gut microbiome remains poorly understood. This study aimed to evaluate the gut microbiome state in infancy following systemic antibiotic treatment. Twenty infants under 3 months of age who had received antibiotics for at least 3 days were enrolled, and their fecal samples were collected 4 weeks after antibiotic administration finished. Thirty-four age-matched healthy controls without prior exposure to antibiotics were also assessed. The relative bacterial abundance in feces was obtained via sequencing of 16 S rRNA genes, and alpha and beta diversities were evaluated. At the genus level, the relative abundance of Escherichia/Shigella and Bifidobacterium increased (p = 0.03 and p = 0.017, respectively) but that of Bacteroides decreased (p = 0.02) in the antibiotic treatment group. The microbiome of the antibiotic treatment group exhibited an alpha diversity lower than that of the control group. Thus, systemic antibiotic administration in early infancy affects the gut microbiome composition even after a month has passed; long-term studies are needed to further evaluate this.

Is High Milk Intake Good for Children's Health? A National Population-Based Observational Cohort Study.

Milk is widely considered as a beneficial product for growing children. This study was designed to describe the milk consumption status of Korean children aged 30-36 months and to investigate its association with the risk of obesity and iron deficiency anemia (IDA). This nationwide administrative study used data from the Korean national health insurance system and child health screening examinations for children born in 2008 and 2009. In total, 425,583 children were included, and they were divided into three groups based on daily milk consumption: low milk group (do not drink or drink <200 mL milk per day, n = 139,659), reference group (drink 200-499 mL milk per day, n = 255,670), and high milk group (drink ≥500 mL milk per day, n = 30,254). After adjusting variable confounding factors, the consumption of a large amount of milk of ≥500 mL per day at the age of 30-36 months was associated with an increased risk of obesity at the age of 42-72 months and IDA after the age of 30 months. These results may provide partial evidence for dietary guidelines for milk consumption in children that are conducive to health.

Serum YKL-40 Levels Are Associated with the Atherogenic Index of Plasma in Children.

YKL-40, also known as chitinase-3-like protein 1, is an inflammatory glycoprotein that is secreted by various cell types under acute, chronic, and subclinical inflammation conditions. Elevated serum YKL-40 levels are reportedly independently related to diabetes mellitus, coronary artery disease, acute myocardial infarction, and cardiovascular mortality in adults. Therefore, we aimed to investigate the relationship between serum YKL-40 levels, lipid abnormalities, and the atherogenic index of plasma (AIP) in children. We enrolled 479 children aged 10-12 years (mean age: 11.52) in this general population-based, cross-sectional study. All subjects completed questionnaires and were subjected to multifrequency bioelectrical impedance analysis (BIA) to measure their height, weight, and body mass index (BMI). We collected serum samples from all participants to measure YKL-40, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Mean serum YKL-40 levels were significantly higher in the low-HDL-C (p = 0.017) and high-TG (p = 0.010) groups but were not related to TC and LDL-C levels. YKL-40 levels were also higher in the high AIP group (p = 0.007). After adjusting for age, gender, and BMI z-score, the associations between serum YKL-40 levels and TG levels (p = 0.003), the TG-to-HDL-C ratio (p = 0.019), and the AIP value (p = 0.012) remained significant. Based on these findings, we suggest that serum YKL-40 may be a useful initial screening tool or follow-up risk indicator for lipid abnormalities, atherosclerosis, and cardiovascular disease in children and adolescents with risk factors, regardless of obesity.

Relative Skeletal Muscle Mass Is an Important Factor in Non-Alcoholic Fatty Liver Disease in Non-Obese Children and Adolescents.

Recently, sarcopenia was identified as a risk factor for non-alcoholic fatty liver disease (NAFLD) in adults. We here investigated the association between skeletal muscle mass (SMM) and NAFLD in non-obese children and adolescents. A retrospective medical chart review was performed for individuals aged 9-15 years diagnosed with NAFLD. Healthy volunteers aged 9-15 years were recruited as controls. Participants were subject to laboratory tests, abdominal sonography, and multi-frequency bioelectrical impedance analysis. SMM data were calculated as the skeletal muscle-to-body fat ratio (MFR), and the diagnosis of fatty liver was established by abdominal sonography. The control and NAFLD groups included 73 and 53 individuals, respectively. No significant difference was observed in gender and body mass index (BMI) distribution between the groups. Mean MFR was significantly lower in individuals with NAFLD than in those without (0.83 vs. 1.04, p = 0.005). After adjusting for age, sex, BMI, and serum glucose, the risk of having NAFLD was significantly associated with a decreased MFR (p = 0.016). NAFLD is significantly associated with relatively low SMM in non-obese children and adolescents. Increasing SMM, such as weight training, can be suggested as one of the treatment strategies in pediatric NAFLD without obesity.

Association between Body Mass Index and Hepatitis B antibody seropositivity in children.

BACKGROUND: The seropositivity rate of hepatitis B surface antigen (anti-HBs) antibodies is known to be ≥95% after hepatitis B virus vaccination during infancy. However, a low level or absence of anti-HBs in healthy children is discovered in many cases. Recent studies in adults reported that a reduced anti-HBs production rate is related to obesity. PURPOSE: To investigate whether body mass index (BMI) affects anti-HBs levels in healthy children following 3 serial dose vaccinations in infancy. METHODS: We recruited 1,200 healthy volunteers aged 3, 5, 7, or 10 years from 4-day care centers and 4 elementary schools. All subjects completed a questionnaire including body weight, height, and vaccine type received. Levels of serum hepatitis B surface antigen (HBsAg) and anti-HBs in all subjects were analyzed using electrochemiluminescence immunoassay. The standardized scores (z score) for each sex and age were obtained using the lambda-mu-sigma method in the 2017 Korean National Growth Charts for children and adolescents. RESULTS: Our subjects (n=1,200) comprised 750 males (62.5%) and 450 females (37.5%). The overall anti-HBs seropositivity rate was 57.9% (695 of 1,200). We identified significant differences in mean BMI values between seronegative and seropositive groups (17.45 vs. 16.62, respectively; P<0.001). The anti-HBs titer was significantly decreased as the BMI z score increased adjusting for age and sex (B=-15.725; standard error=5.494; P=0.004). The probability of anti-HBs seropositivity based on BMI z score was decreased to an OR of 0.820 after the control for confounding variables (95% confidence interval, 0.728-0.923; P=0.001). CONCLUSION: There was a significant association between anti-HBs titer and BMI z score after adjustment for age and sex. Our results indicate that BMI is a potential factor affecting anti-HBs titer in healthy children.